US5643874A - Pharmaceutical composition comprising a glucosidase and/or amylase inhibitor, and a lipase inhibitor - Google Patents

Pharmaceutical composition comprising a glucosidase and/or amylase inhibitor, and a lipase inhibitor Download PDF

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US5643874A
US5643874A US08/279,127 US27912794A US5643874A US 5643874 A US5643874 A US 5643874A US 27912794 A US27912794 A US 27912794A US 5643874 A US5643874 A US 5643874A
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inhibitor
glucopyranosyl
glucosidase
dideoxy
methyl
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Klaus-Dieter Bremer
Pavel Sawlewicz
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Hoffmann La Roche Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate

Definitions

  • the invention relates to pharmaceutical compositions containing an effective amount of at least one but no more than two glucosidase and/or amylase inhibitors and a lipase inhibitor as active substances; and the usual pharmaceutical carriers.
  • the invention relates to the use of at least one but no more than two glucosidase and/or amylase inhibitors for the combined simultaneous, separate or chronologically spaced use with a lipase inhibitor in the treatment of obesity.
  • the invention is also concerned with the use of at least one but no more than two glucosidase and/or amylase inhibitors for the combined simultaneous, separate or chronologically spaced use with a lipase inhibitor in the treatment of obesity.
  • the invention is concerned with the use of at least one but no more than two glucosidase and/or amylase inhibitors in the manufacture of pharmaceutical compositions for the combined use with a lipase inhibitor in the treatment of obesity.
  • glucosidase and/or amylase inhibitors examples include:
  • N-[3-chloro-4-(trifluoromethyl)phenyl-]N'-[3-(trifluoromethyl)-phenyl]urea also known as BAY-N-3176;
  • 1,6-di(O-(carbamoyl)cyclohexanone oxime)hexane also known as RHC 80267.
  • Biomasses or fermentation cakes which result in the fermentative manufacture of lipase inhibitors such as, (2S,3S,5S, 7Z,10Z)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-7,10-hexadecadienoic 1,3 acid lactone also known as lipstatin or (2S,3S,5S,7Z,10Z)-5-[(S)-2-acetamido-3-carbamoyl-propionyloxy]-2-hexyl-3-hydroxy-7,10-hexadecadienoic lactone also known as esterastin, can also be used as the lipase inhibitor.
  • the latter are described, for example, in EP-A 129 748 and U.S. Pat. No. 4,189,438.
  • glucosidase inhibitors or amylase inhibitors or both such as, O-4,6-dideoxy-4-[[[1S-(1 ⁇ ,4 ⁇ ,5 ⁇ ,6 ⁇ )]-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino]- ⁇ -D-glucopyranosyl-(1.fwdarw.4)O- ⁇ -D-glucopyranosyl-(1 ⁇ 4)-D-glucose also known as acarbose, retard the digestion of carbohydrates.
  • lipase inhibitors such as, (2S,3S,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone also known as tetrahydrolipstatin, give rise to a partial inhibition of lipase in the intestine.
  • the test was carried out in two trial periods on two volunteers (A and B).
  • the average daily calorie amounts of 2560 Kcal for A and 1850 Kcal for B were determined in a 7 day preliminary trial in which the volunteers took no medication.
  • the volunteers were given 120 mg of (2S,3S,5S)-5-[(S)-2-formamido 4-methyl-is valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone also known as tetrahydrolipstatin and 100 mg of O-4,6-dideoxy-4-[[[1S-(1 ⁇ ,4 ⁇ ,5 ⁇ ,6 ⁇ )]-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino]- ⁇ -D-glucopyranosyl-(1.fwdarw.4) O- ⁇ -D-glucopyranosyl-(1 ⁇ 4)-D-glucose also known as acarbose at each meal time in the
  • At least one but no more than two inhibitors of the glucosidase and/or amylase can be used in the form of pharmaceutical compositions in combination with a lipase inhibitor for the simultaneous, separate or chronologically spaced use in the treatment of obesity.
  • the active ingredients are administered orally for the treatment of obesity.
  • They can be administered daily in dosages of about 0.003 mg to about 20 mg, preferably 0.015 mg to 10 mg, of glucosidase and/or amylase inhibitor and of about 0.15 mg to 20 mg, preferably 0.5 mg to 10 mg, of lipase inhibitor per kg body weight.
  • compositions in accordance with the invention, can be incorporated into standard pharmaceutical dosage forms, for example, they are useful for oral application with the usual pharmaceutical adjuvant material, for example, organic or inorganic inert carrier materials, such as, water, gelatin, lactose, starch, magnesium stearate, talc, gums, polyalkyleneglycols and the like.
  • pharmaceutical adjuvant material for example, organic or inorganic inert carrier materials, such as, water, gelatin, lactose, starch, magnesium stearate, talc, gums, polyalkyleneglycols and the like.
  • the pharmaceutical preparations can be employed in a solid form, for example, as tablets, capsules, or in liquid form, for example, as solutions, or emulsions.
  • Pharmaceutical adjuvant materials can be added and include preservatives, stabilizers, wetting or emulsifying agents, salts to change the osmotic pressure or to act as buffers.
  • the pharmaceutical preparations can also contain
  • Solid dosage forms such as tablets and capsules conveniently contain per dosage unit about 0.2 mg to about 100 mg of glucosidase and/or amylase inhibitor and 10 mg to 200 mg of lipase inhibitor.
  • compositions or active substance combination in accordance with the invention, can be used for the treatment and prevention of illnesses which frequently occur in association with overweight, such as diabetes, hypertension, hyperlipidemia and insulin-resistance syndrome.
  • the active substances can be used in the dosage ranges given above, with the individual dosage depending on the nature of the illness to be treated as well as on the age and condition of the patient and can be determined within the purview of the medical specialist.
  • compositions of the following composition are produced in a known manner:
  • Examples A-E can be prepared by known methods.

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  • General Health & Medical Sciences (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Child & Adolescent Psychology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract

A pharmaceutical composition containing a glucosidase and/or amylase inhibitor and a lipase inhibitor as active substances and usual pharmaceutical carriers.

Description

BRIEF SUMMARY OF THE INVENTION
The invention relates to pharmaceutical compositions containing an effective amount of at least one but no more than two glucosidase and/or amylase inhibitors and a lipase inhibitor as active substances; and the usual pharmaceutical carriers.
In another aspect, the invention relates to the use of at least one but no more than two glucosidase and/or amylase inhibitors for the combined simultaneous, separate or chronologically spaced use with a lipase inhibitor in the treatment of obesity.
DETAILED DESCRIPTION OF THE INVENTION
It has been found that such preparations can be used for the treatment of obesity.
Accordingly, the invention is also concerned with the use of at least one but no more than two glucosidase and/or amylase inhibitors for the combined simultaneous, separate or chronologically spaced use with a lipase inhibitor in the treatment of obesity.
Further, the invention is concerned with the use of at least one but no more than two glucosidase and/or amylase inhibitors in the manufacture of pharmaceutical compositions for the combined use with a lipase inhibitor in the treatment of obesity.
Examples of known glucosidase and/or amylase inhibitors which can be used, in accordance with the invention are:
O-4,6-dideoxy-4-[[[1S-(1α,4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1.fwdarw.4)O-α-D-glucopyranosyl-(1→4)-D-glucose, also known as acarbose;
2(S),3(R) ,4(S),5(S)-tetrahydroxy-N-[2-hydroxy-1-(hydroxymethyl)-ethyl]-5-(hydroxymethyl)-1(S)-cyclohexamine, also known as voglibose;
1,5-dideoxy-1,5-[(2-hydroxyethyl)imino]-D-glucitol, also known as miglitol;
1,5-dideoxy-1,5-[2-(4-ethoxycarbonylphenoxy)ethylimino]-D-glucitol, also known as emiglitate;
2,6-dideoxy-2,6-imino-7-(β-D-glucopyranosyl)-D-glycero-L-guloheptitol, also known as MDL-25637;
1,5-dideoxy-1,5-(6-deoxy-1-O-methyl-α-D-glucopyranos-6-ylimino)-D-glucitol, also known as camiglibose;
1,5,9,11,14-pentahydroxy-3-methyl-8,13-dioxo-5,6,8,13-tetrahydrobenzo[a]naphthacene-2-carboxylic acid, also known pradimicin Q; ##STR1## wherein m is an integer of 0 to 8, n is an integer of 1 to 8 and m+n is an integer of 1 to 8, also known as adiposine; and
1,2-dideoxy-2-[2(S),3(S),4(R)-trihydroxy-5-(hydroxymethyl)-5-cyclohexen-1(S)-ylamino]-L-glucopyranose, also known as salbostatin.
Examples of known lipase inhibitors are:
(2S,3S ,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone, also known as tetrahydrolipstatin (previously also known as Orlistat);
(2S ,3S,5S,7Z, 10Z)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-7,10-hexadecadienoic 1,3 acid lactone, also known as lipstatin;
1-(trans-4-isobutylcyclohexyl)-2-(phenylsulfonyloxy)ethanone, also known as FL-386;
4-methylpiperidine-1-carboxylic acid 4-phenoxyphenyl ester, also known as WAY-121898;
N-[3-chloro-4-(trifluoromethyl)phenyl-]N'-[3-(trifluoromethyl)-phenyl]urea, also known as BAY-N-3176;
N-formyl-L-valine-(S)-1 -[[(2S, 3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]hexyl ester, also known as valilactone;
(2S,3S,5S,7Z,10Z)-5-[(S)-2-acetamido-3-carbamoylpropionyloxy]-2-hexyl-3-hydroxy-7,10-hexadecadienoic lactone, also known as esterastin;
(3S,4S)-4-[(1S,5R,7S,8R,9R,E)-8-hydroxy 1,3,5,7,9-pentamethyl-6-oxo-3-undecenyl]-3-methyl-2-oxetanone, also known as ebelactone A;
(3S,4S)-3-ethyl-4-[(1S,5R,7S,8R,9R,E)-8-hydroxy-1,3,5,7,9-pentamethyl-6-oxo-3-undecenyl]-2-oxetanone, also known as ebelactone B; and
1,6-di(O-(carbamoyl)cyclohexanone oxime)hexane, also known as RHC 80267.
Biomasses or fermentation cakes which result in the fermentative manufacture of lipase inhibitors, such as, (2S,3S,5S, 7Z,10Z)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-7,10-hexadecadienoic 1,3 acid lactone also known as lipstatin or (2S,3S,5S,7Z,10Z)-5-[(S)-2-acetamido-3-carbamoyl-propionyloxy]-2-hexyl-3-hydroxy-7,10-hexadecadienoic lactone also known as esterastin, can also be used as the lipase inhibitor. The latter are described, for example, in EP-A 129 748 and U.S. Pat. No. 4,189,438.
It is known that either glucosidase inhibitors or amylase inhibitors or both, such as, O-4,6-dideoxy-4-[[[1S-(1α,4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1.fwdarw.4)O-α-D-glucopyranosyl-(1→4)-D-glucose also known as acarbose, retard the digestion of carbohydrates.
It is also known that lipase inhibitors, such as, (2S,3S,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone also known as tetrahydrolipstatin, give rise to a partial inhibition of lipase in the intestine.
However, in monotherapy lipase inhibitors themselves in combination with a reduction diet generally bring about only a moderate weight loss and glucosidase and/or amylase inhibitors bring about practically no weight loss. It has now been surprisingly found that a combined use of a glucosidase and/or amylase inhibitor and a lipase inhibitor leads to a substantially greater weight loss than in the case of monotherapy. This has been demonstrated in the following test:
The test was carried out in two trial periods on two volunteers (A and B). The average daily calorie amounts of 2560 Kcal for A and 1850 Kcal for B were determined in a 7 day preliminary trial in which the volunteers took no medication. The volunteers were given 120 mg of (2S,3S,5S)-5-[(S)-2-formamido 4-methyl-is valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone also known as tetrahydrolipstatin and 100 mg of O-4,6-dideoxy-4-[[[1S-(1α,4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1.fwdarw.4) O-α-D-glucopyranosyl-(1→4)-D-glucose also known as acarbose at each meal time in the subsequent 14 day main trial. A special diet was not adhered to and physical activities were reduced to a minimum. Here, as in the preliminary trial, the average daily calorie amounts of 2185 Kcal for A and 2050 Kcal for B were also ascertained. The weight loss of both volunteers will be evident from the following Table.
______________________________________                                    
               Body weight                                                
Trial day        A      B                                                 
______________________________________                                    
1                74.3   88.7                                              
2                74.1   88.5                                              
3                74.6   89.1                                              
4                73.9   88.0                                              
5                73.5   88.4                                              
6                73.3   88.2                                              
7                73.0   87.7                                              
8                73.6   87.8                                              
9                73.3   87.7                                              
10               73.1   87.4                                              
11               72.8   87.2                                              
12               72.4   87.5                                              
13               72.4   87.2                                              
14               72.2   86.4                                              
15               71.9   86.1                                              
Weight loss      2.4    2.6                                               
______________________________________
In comparison to the above result, the weight loss of patients in the case of monotherapy with tetrahydrolipstatin (3×120 mg/day) in a placebo-controlled 12 weeks trial was on average 1.8 kg (i.e. 0.3 kg/14 days) (Int. J. Obesity 1992; 16 (Suppl. 1): 16, Abstr. 063).
In accordance with the invention, at least one but no more than two inhibitors of the glucosidase and/or amylase can be used in the form of pharmaceutical compositions in combination with a lipase inhibitor for the simultaneous, separate or chronologically spaced use in the treatment of obesity.
The use of O-4,6-dideoxy-4-[[[1S-(1α,4α,5β,6α, )]-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1→4)O-α-D-glucopyranosyl-(1→4)-D-glucose also known as acarbose and (2S,3S,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone also known as tetrahydrolipstatin is preferred.
The active ingredients are administered orally for the treatment of obesity.
They can be administered daily in dosages of about 0.003 mg to about 20 mg, preferably 0.015 mg to 10 mg, of glucosidase and/or amylase inhibitor and of about 0.15 mg to 20 mg, preferably 0.5 mg to 10 mg, of lipase inhibitor per kg body weight.
The compositions, in accordance with the invention, can be incorporated into standard pharmaceutical dosage forms, for example, they are useful for oral application with the usual pharmaceutical adjuvant material, for example, organic or inorganic inert carrier materials, such as, water, gelatin, lactose, starch, magnesium stearate, talc, gums, polyalkyleneglycols and the like. The pharmaceutical preparations can be employed in a solid form, for example, as tablets, capsules, or in liquid form, for example, as solutions, or emulsions. Pharmaceutical adjuvant materials can be added and include preservatives, stabilizers, wetting or emulsifying agents, salts to change the osmotic pressure or to act as buffers. The pharmaceutical preparations can also contain other therapeutically active substances.
Solid dosage forms such as tablets and capsules conveniently contain per dosage unit about 0.2 mg to about 100 mg of glucosidase and/or amylase inhibitor and 10 mg to 200 mg of lipase inhibitor.
In addition to the treatment of obesity, the compositions or active substance combination, in accordance with the invention, can be used for the treatment and prevention of illnesses which frequently occur in association with overweight, such as diabetes, hypertension, hyperlipidemia and insulin-resistance syndrome.
In the case of all of these indications, the active substances can be used in the dosage ranges given above, with the individual dosage depending on the nature of the illness to be treated as well as on the age and condition of the patient and can be determined within the purview of the medical specialist.
The invention is illustrated in more detail by the following Examples.
Pharmaceutical compositions of the following composition are produced in a known manner:
EXAMPLE A 
______________________________________                                    
Soft gelatin capsules                                                     
                Amount per capsule                                        
______________________________________                                    
Tetrahydrolipstatin                                                       
                  60         mg                                           
Medium chain triglyceride                                                 
                  450        μl                                        
Acarbose          50         mg                                           
______________________________________
EXAMPLE B 
______________________________________                                    
Hard gelatin capsules                                                     
Acarbose            25.0       mg                                         
Tetrahydrolipstatin 30.0       mg                                         
Cryst. lactose      37.0       mg                                         
Microcrystalline cellulose                                                
                    20.0       mg                                         
Polyvinylpolypyrrolidone                                                  
                    8.5        mg                                         
Sodium carboxymethylstarch                                                
                    8.5        mg                                         
Talc                4.5        mg                                         
Magnesium stearate  1.5        mg                                         
Capsule fill weight 135.0      mg                                         
______________________________________                                    

______________________________________                                    
Tablets                                                                   
Acarbose                25.0   mg                                         
Tetrahydrolipstatin     30.0   mg                                         
Anhydrous lactose       118.8                                             
Microcrystalline cellulose                                                
                        30.0                                              
Polyvinylpolypyrrolidone                                                  
                        10.0                                              
Carboxymethylcellulose  10.0                                              
Magnesium stearate      1.2                                               
Tablet weight           225.0  mg                                         
______________________________________
EXAMPLE D 
______________________________________                                    
Tablets having controlled active substance release and                    
increased residence time in the stomach                                   
Acarbose                50.0   mg                                         
Tetrahydrolipstatin     60.0   mg                                         
Powd. lactose           70.0   mg                                         
Hydroxypropylmethylcellulose                                              
                        52.5   mg                                         
Polyvinylpolypyrrolidone                                                  
                        7.5    mg                                         
Talc                    8.0    mg                                         
Magnesium stearate      1.0    mg                                         
Colloidal silicic acid  1.0    mg                                         
Core weight             250.0  mg                                         
______________________________________                                    
Hydroxypropylmethylcellulose                                              
                        2.5    mg                                         
Talc                    1.25   mg                                         
Titanium dioxide        1.25   mg                                         
Film coating weight     5.0    mg                                         
______________________________________
EXAMPLE E 
______________________________________                                    
Powder for reconstitution                                                 
Acarbose                100.0   mg                                        
Tetrahydrolipstatin     120.0   mg                                        
Ethylvanillin           10.0    mg                                        
Aspartame               30.0    mg                                        
Sprayed skimmed milk powder                                               
                        4740.0  mg                                        
Total                   5000.0  mg                                        
______________________________________
The formulation of Examples A-E can be prepared by known methods.
__________________________________________________________________________
SEQUENCE LISTING                                                          
(1) GENERAL INFORMATION:                                                  
(iii) NUMBER OF SEQUENCES: 2                                              
(2) INFORMATION FOR SEQ ID NO:1:                                          
(i) SEQUENCE CHARACTERISTICS:                                             
(A) LENGTH: 74 amino acids                                                
(B) TYPE: amino acid                                                      
(C) STRANDEDNESS: single                                                  
(D) TOPOLOGY: linear                                                      
(ii) MOLECULE TYPE: peptide                                               
(iii) HYPOTHETICAL: NO                                                    
(iv) ANTI-SENSE: NO                                                       
(vi) ORIGINAL SOURCE:                                                     
(A) ORGANISM: Streptomyces tendae                                         
(ix) FEATURE:                                                             
(A) NAME/KEY: Disulfide-bond                                              
(B) LOCATION: 11..27                                                      
(ix) FEATURE:                                                             
(A) NAME/KEY: Disulfide-bond                                              
(B) LOCATION: 45..73                                                      
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:                                   
AspThrThrValSerGluProAlaProSerCysValThrLeuTyrGln                          
151015                                                                    
SerTrpArgTyrSerGlnAlaAspAsnGlyCysAlaGluThrValThr                          
202530                                                                    
ValLysValValTyrGluAspAspThrGluGlyLeuCysTyrAlaVal                          
354045                                                                    
AlaProGlyGlnIleThrThrValGlyAspGlyTyrIleGlySerHis                          
505560                                                                    
GlyHisAlaArgTyrLeuAlaArgCysLeu                                            
6570                                                                      
(2) INFORMATION FOR SEQ ID NO:2:                                          
(i) SEQUENCE CHARACTERISTICS:                                             
(A) LENGTH: 36 amino acids                                                
(B) TYPE: amino acid                                                      
(C) STRANDEDNESS: double                                                  
(D) TOPOLOGY: both                                                        
(ii) MOLECULE TYPE: peptide                                               
(iii) HYPOTHETICAL: NO                                                    
(iv) ANTI-SENSE: NO                                                       
(v) FRAGMENT TYPE: N-terminal                                             
(vi) ORIGINAL SOURCE:                                                     
(A) ORGANISM: Streptomyces aureofaciens                                   
(B) STRAIN: FH1656                                                        
(ix) FEATURE:                                                             
(A) NAME/KEY: Cross-links                                                 
(B) LOCATION: 8..25                                                       
(ix) FEATURE:                                                             
(A) NAME/KEY: Cross-links                                                 
(B) LOCATION: 9..26                                                       
(ix) FEATURE:                                                             
(A) NAME/KEY: Peptide                                                     
(B) LOCATION: 1..19                                                       
(ix) FEATURE:                                                             
(A) NAME/KEY: Peptide                                                     
(B) LOCATION: 20..36                                                      
(ix) FEATURE:                                                             
(A) NAME/KEY: Cross-links                                                 
(B) LOCATION: 20..36                                                      
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:                                   
AlaThrGlySerProAlaProAspSerAspAlaValThrValValVal                          
151015                                                                    
GlnTyrGluGlnPheSerGluValCysCysGlyAsnArgValAspThr                          
202530                                                                    
TyrArgTrpSer                                                              
35                                                                        
__________________________________________________________________________

Claims (22)

We claim:
1. A pharmaceutical composition which comprises an effective amount of a lipase inhibitor and (a) a glucosidase inhibitor, (b) an amylase inhibitor or, (c) a glucosidase and amylase inhibitor, together with an inert carrier.
2. A pharmaceutical composition according to claim 1, wherein the daily dosage of a lipase inhibitor is 0.15 to 20 mg per Kg body weight and the daily dosage of said glucosidase inhibitor, amylase inhibitor or glucosidase and amylase inhibitor is 0.003 to 20 mg per Kg body weight.
3. A pharmaceutical composition according to claim 1, in the form of a solid dosage unit comprising per dosage unit 10 to 200 mg of a lipase inhibitor and 0.2 to 100 mg of said glucosidase inhibitor, amylase inhibitor or glucosidase and amylase inhibitor.
4. A pharmaceutical composition according to claim 2, wherein the lipase inhibitor is selected from the group consisting of (2S ,3S ,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone, (2S,3S,5S,7Z,10Z)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-7,10-hexadecadienoic 1,3 acid lactone, 1-(trans-4-isobutylcyclohexyl)-2-(phenylsulfonyloxy) ethanone, 4-methylpiperidine-1-carboxylic acid 4-phenoxyphenyl ester, N-[3-chloro-4-(trifluoromethyl)phenyl-N'-[3-(trifluoromethyl)phenyl]urea; N-formyl-L-valine-(S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]hexyl ester, (2S ,3S, 5S,7Z,10Z)-5-[(S)-2-acetamido-3-carbamoylpropionyloxy]-2-hexyl-3-hydroxy-7,10-hexadecadienoic lactone, (3S,4S)-4-[(1S,5R,7S,8R,9R,E)-8-hydroxy-1,3,5,7,9-pentamethyl-6-oxo-3-undecenyl]-3-methyl-2-oxetanone, (3S,4S)-3-ethyl-4-[(1S,5R, 7S,8R,9R,E)-8-hydroxy-1,3,5,7,9-pentamethyl-6-oxo-3-undecenyl]-2-oxetanone, and 1,6-di(O-(carbamoyl)cyclohexanone oxime)hexane.
5. A pharmaceutical composition according to claim 2, wherein the lipase inhibitor is (2S,3S,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone.
6. A method for treating obesity which comprises administering to a host in need of such treatment an effective amount of a lipase inhibitor and (a) glucosidase inhibitor, (b) amylase inhibitor, (c) or a glucosidase and amylase inhibitor.
7. A method for treating obesity which comprises administering a lipase inhibitor and (a) a glucosidase inhibitor, (b) amylase inhibitor, or (c) a glucosidase and amylase inhibitor in a simultaneous, separate, or chronologically spaced manner.
8. A method according to claim 6, wherein the daily dosage of lipase inhibitor is 0.15 to 20 mg per Kg body weight and the daily dosage of said glucosidase inhibitor, amylase inhibitor or glucosidase and amylase inhibitor is 0.003 to 20 mg per Kg body weight.
9. A method according to claim 6, wherein the lipase inhibitor and (a) glucosidase inhibitor, (b) amylase inhibitor, or (c) glucosidase and amylase inhibitor are administered in a solid dosage unit comprising per dosage unit 10 to 200 mg of lipase inhibitor and 0.2 to 100 mg of the (a) glucosidase inhibitor, (b) amylase inhibitor, or (c) glucosidase and amylase inhibitor.
10. A method according to claim 7, wherein the lipase is inhibitor is selected from the group consisting of (2S,3S,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone, (2S,3S,5S, 7Z,10Z)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-7,10-hexadecadienoic 1,3 acid lactone, 1-(trans-4-isobutylcyclohexyl)-2-(phenyl-sulfonyloxy)ethanone, 4-methyl-piperidine-1-carboxylic acid 4-phenoxyphenyl ester, N-[3-chloro-4-(trifluoromethyl)phenyl-N'-[3-(trifluoromethyl)phenyl]urea, N-formyl-L-valine-(S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]hexyl ester, (2S ,3S,5S ,7Z, 10Z)-5-[(S)-2-acetamido-3-carbamoyl-propionyloxy]-2-hexyl-3-hydroxy-7,10-hexadecadienoic lactone, (3S,4S)-4-[(1S,5R,7S,8R,9R,E)-8-hydroxy-1,3,5,7,9-pentamethyl-6-oxo-3-undecenyl]-3-methyl-2-oxetanone, (3S,4S)-3-ethyl-4-[(1S,5R,7S, 8R,9R,E)-8-hydroxy-1,3,5,7,9-pentamethyl-6-oxo-3-undecenyl]-2-oxetanone, and 1,6-di(O-(carbamoyl)cyclohexanone oxime)hexane.
11. A pharmaceutical composition according to claim 2, wherein the (a) glucosidase inhibitor, (b) amylase inhibitor or (c) glucosidase and amylase inhibitor is selected from the group consisting of O-4,6-Dideoxy-4-[[[1S-(1α,4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1.fwdarw.4) O-α-D-glucopyranosyl-(1→4)-D-glucose, 2(S),3(R),4(S),5(S)-tetrahydroxy-N-[2-hydroxy-1-(hydroxymethyl)-ethyl]-5-(hydroxymethyl)-1(S)-cyclohexamine, 1,5-dideoxy-1,5-[(2-hydroxyethyl)imino]-D-glucitol,1,5-dideoxy-1,5-[2-(4-ethoxy-carbonylphenoxy)ethylimino]-D-glucitol, 2,6-dideoxy-2,6-imino-7-(β-D-glucopyranosyl)-D-glycero-L-gulo-heptitol, 1,5-dideoxy-1,5-(6-deoxy-1-O-methyl-α-D-glucopyranos-6-ylimino)-D-glucitol, ##STR2## wherein m is an integer of 0 to 8, n is an integer of 1 to 8 and m+n is an integer of 1 to 8,
1. 5,9,11,14-pentahydroxy-3-methyl-8,13-dioxo-5,6,8,13-tetrahydrobenzo[a]naphthacene-2-carboxylic acid, and 1,2-dideoxy-2-[2(S),3(S),4(R)-trihydroxy-5-(hydroxymethyl)-5-cyclohexen-1(S)-ylamino]-L-glucopyranose.
12. A pharmaceutical composition according to claim 2, wherein the (a) glucosidase inhibitor, (b) amylase inhibitor, or (c) glucosidase and amylase inhibitor is O-4,6-dideoxy-4-[[[1S-(1α,4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1.fwdarw.4) O-α-D-glucopyranosyl-(1→4)-D-glucose.
13. A method according to claim 7, wherein the (a) glucosidase inhibitor, (b) amylase inhibitor, or (c) glucosidase and amylase inhibitor is selected from the group consisting of O-4,6-dideoxy-4-[[[1S-(1α,4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1.fwdarw.4) O-α-D-glucopyranosyl-(1→4)-D-glucose, 2(S),3(R),4(S),5(S)-tetrahydroxy-N-[2-hydroxy-1-(hydroxymethyl)ethyl]-5-(hydroxymethyl)-1(S)-cyclohexamine, 1,5-dideoxy-1,5-[(2-hydroxyethyl)imino]-D-glucitol,1,5-dideoxy-,1,5-[2-(4-ethoxy-carbonylphenoxy)ethylimino]-D-glucitol, 2,6-dideoxy-2,6-imino-7-(β-D-glucopyranosyl)-D-glycero-L-gulo-heptitol, 1,5-dideoxy-,1,5-(6-deoxy-1-O-methyl-α-D-glucopyranos-6-ylimino)-D-glucitol, ##STR3## wherein m is an integer of 0 to 8, n is an integer of 1 to 8 and m+n is an integer of 1 to 8, 1,5,9,11,14-pentahydroxy-3-methyl-8,13-dioxo-5,6,8,13-tetrahydrobenzo[a]naphthacene-2-carboxylic acid, and 1,2-dideoxy-2-[2(S),3(S),4(R)-trihydroxy-5-(hydroxymethyl)-5-cyclohexen-1(S)-ylamino]-L-glucopyranose.
14. A method according to claim 7, wherein the (a) glucosidase inhibitor, (b) amylase inhibitor, or (c) glucosidase and amylase inhibitor is O-4,6-dideoxy-4-[[[1S-(1α,4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1.fwdarw.4) O-α-D-glucopyranosyl-(1→4)-D-glucose.
15. A pharmaceutical composition which comprises an effective amount of (2S,3S,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 and lactone; O-4,6-dideoxy -4-[[[1S-(1α4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1→4) O-α-D-glucopyranosyl-(1→4)-D-glucose and an inert carrier.
16. A pharmaceutical composition according to claim 15, wherein the daily dosage of (2S,3S,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone is 0.15 to 20 mg per kg body weight and the daily dosage of O-4,6-dideoxy-4-[[[1S-(1α,4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1.fwdarw.4) O-α-D-glucopyranosyl-(1→4)-D-glucose is 0.003 to 20 mg per kg body weight.
17. A pharmaceutical composition according to claim 15, in the form of a solid dosage unit comprising per dosage unit 10 to 200 mg of (2S,3 S,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone and 0.2 to 100 mg of O-4,6-dideoxy-4-[[[1S-(1α,4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1.fwdarw.4) O-α-D-glucopyranosyl-(1→4)-D-glucose.
18. A method for treating obesity which comprises administering to a host in need of such treatment an effective amount of (2S,3S,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone and O-4,6-dideoxy-4-[[[1S-(1α,4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1.fwdarw.4) O-α-D-glucopyranosyl-(1→4)-D-glucose.
19. A method for treating obesity which comprises administering to a host in need of such treatment (2S,3S,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone and O-4,6-dideoxy-4-[[[1S-(1α,4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1.fwdarw.4) O-α-D-glucopyranosyl-(1→4)-D-glucose in a simultaneous, separate, or chronologically spaced manner.
20. A method according to claim 18, wherein the daily dosage of (2S,3S,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone is 0.15 to 20 mg per kg body weight and the daily dosage of O-4,6-dideoxy-4-[[[1S-(1α,4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1.fwdarw.4) O-α-D-glucopyranosyl-(1→4)-D-glucose is 0.003 to 20 mg per kg body weight.
21. A method according to claim 18, wherein (2S,3S,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone and O-4,6-dideoxy-4-[[[1S-(1α,4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1.fwdarw.4) O-α-D-glucopyranosyl-(1→4)-D-glucose are administered in a solid dosage unit comprising per dosage unit 10 to 200 mg of (2S,3S,5S)-5-[(S)-2-formamido-4-methyl-valeryloxy]-2-hexyl-3-hydroxy-hexadecanoic 1,3 acid lactone and 0.2 to 100 mg of O-4,6-dideoxy-4-[[[1S-(1α,4α,5β,6α)]-4,5,6-trihydroxy-3-(hydroxymethyl-2-cyclohexen-1-yl]amino]-α-D-glucopyranosyl-(1.fwdarw.4) O-α-D-glucopyranosyl-(1→4)-D-glucose.
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Cited By (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6004996A (en) * 1997-02-05 1999-12-21 Hoffman-La Roche Inc. Tetrahydrolipstatin containing compositions
WO2000013667A1 (en) * 1998-09-08 2000-03-16 Smithkline Beecham Corporation Lipstatin derivative-soluble fiber tablets
US6147108A (en) * 1997-02-05 2000-11-14 Hoffman-La Roche Inc. Method for treating type II diabetes mellitus
WO2001032669A1 (en) * 1999-10-29 2001-05-10 John Jason Gentry Mullins Oxetanone derivatives
WO2001032670A1 (en) * 1999-10-29 2001-05-10 John Jason Gentry Mullins Oxetanone derivatives
US6235305B1 (en) * 1999-10-29 2001-05-22 2Pro Chemical Essentially nonabsorbable lipase inhibitor derivatives, pharmaceutical compositions and methods of use therefor
WO2000043036A3 (en) * 1999-01-22 2001-11-01 Hunza Di Maria Carmela Marazzi Lipoprotein complexes and compositions containing them
US6342519B2 (en) * 1999-10-29 2002-01-29 2 Pro Chemical Oxetanone derivatives
US6358522B1 (en) * 1998-08-14 2002-03-19 Hoffmann-La Roche Inc. Pharmaceutical compositions containing lipase inhibitor
WO2002009815A3 (en) * 2000-07-28 2002-04-18 Hoffmann La Roche New pharmaceutical composition
WO2002009814A3 (en) * 2000-07-28 2002-04-18 Hoffmann La Roche New use of lipase inhibitors
US6403641B2 (en) 1997-12-24 2002-06-11 Abbott Labortories Therapeutic agents
KR100349334B1 (en) * 1999-12-08 2002-08-21 박관화 Anti-obese compound with hypoglycemic activity and prepartion method thereof
WO2002083153A1 (en) * 2001-04-10 2002-10-24 Morrison James U Method and composition for controlled release acarbose formulations
US20040091554A1 (en) * 2002-11-07 2004-05-13 Murray Mary A. Nutritional supplement containing alpha-glucosidase and alpha-amylase inhibitors
RU2229289C2 (en) * 1999-06-24 2004-05-27 Кнолль Гмбх Pharmaceutical composition containing sibutramine and orlistat
US20040175420A1 (en) * 1999-09-13 2004-09-09 De Smidt Passchier Christiaan Pharmaceutical compositions containing lipase inhibitors
US20060029567A1 (en) * 2004-08-04 2006-02-09 Bki Holding Corporation Material for odor control
US20060111422A1 (en) * 2004-11-23 2006-05-25 Warner-Lambert Company Llc Novel pyrazole-based HMG CoA reductase inhibitors
US20060202077A1 (en) * 2004-05-07 2006-09-14 Enventys, Llc Independently drawing and tensioning lines with bi-directional rotary device having two spools
US20060229261A1 (en) * 2005-04-12 2006-10-12 John Devane Acarbose methods and formulations for treating chronic constipation
WO2006119038A1 (en) * 2005-04-29 2006-11-09 Naturegen, Inc. Compositions and methods for controlling glucose uptake
US20060293233A1 (en) * 2005-02-04 2006-12-28 The Research Foundation Of State University Of New York Compositions and methods for modulating body weight and treating obesity-related disorders
US20070104805A1 (en) * 2005-11-01 2007-05-10 Udell Ronald G Compositions of Hoodia Gordonii and Pinolenic Acid Derivatives
WO2007062314A2 (en) 2005-11-23 2007-05-31 Bristol-Myers Squibb Company Heterocyclic cetp inhibitors
WO2008059335A1 (en) 2006-11-13 2008-05-22 Pfizer Products Inc. Diaryl, dipyridinyl and aryl-pyridinyl derivatives and uses thereof
WO2008070496A2 (en) 2006-12-01 2008-06-12 Bristol-Myers Squibb Company N- ( (3-benzyl) -2, 2- (bis-phenyl) -propan-1-amine derivatives as cetp inhibitors for the treatment of atherosclerosis and cardiovascular diseases
US20080182851A1 (en) * 2006-11-20 2008-07-31 Glenmark Pharmaceuticals S.A. Acetylene derivatives as stearoyl coa desaturase inhibitors
US20080269233A1 (en) * 2005-08-04 2008-10-30 Mark David Andrews Piperidinoyl-Pyrrolidine and Piperidinoyl-Piperidine Compounds
US20090036459A1 (en) * 2006-02-23 2009-02-05 Pfizer Inc Melanocortin Type 4 Receptor Agonist Piperidinoylpyrrolidines
WO2009037542A2 (en) 2007-09-20 2009-03-26 Glenmark Pharmaceuticals, S.A. Spirocyclic compounds as stearoyl coa desaturase inhibitors
US20090208584A1 (en) * 2005-06-09 2009-08-20 Tomohiro Yoshinari Solid preparation
US7649002B2 (en) 2004-02-04 2010-01-19 Pfizer Inc (3,5-dimethylpiperidin-1yl)(4-phenylpyrrolidin-3-yl)methanone derivatives as MCR4 agonists
US7713546B1 (en) 2001-04-03 2010-05-11 Soft Gel Technologies, Inc. Corosolic acid formulation and its application for weight-loss management and blood sugar balance
US20100210633A1 (en) * 2006-10-12 2010-08-19 Epix Delaware, Inc. Carboxamide compounds and their use
US20100261661A1 (en) * 2007-09-12 2010-10-14 University Of Copenhagen Compositions and methods for increasing the suppression of hunger and reducing the digestibility of non-fat energy satiety
US20110136814A1 (en) * 2008-08-06 2011-06-09 Mark David Andrews Diazepine and Diazocane Compounds As MC4 Agonists
WO2011145022A1 (en) 2010-05-21 2011-11-24 Pfizer Inc. 2-phenyl benzoylamides
EP2392567A1 (en) 2005-10-21 2011-12-07 Bristol-Myers Squibb Company Benzothiazine derivatives and their use as lxr modulators
US8252312B1 (en) * 2011-12-27 2012-08-28 David Wong Oral solid composition comprising a lipid absorption inhibitor
WO2012120414A2 (en) 2011-03-04 2012-09-13 Pfizer Inc. Edn3-like peptides and uses thereof
US20120276081A1 (en) * 2010-02-25 2012-11-01 Fujifilm Corporation Body weight gain suppressing composition and food product comprising the same
WO2013133685A1 (en) 2012-03-09 2013-09-12 Biotropics Malaysia Berhad Extract formulations of rhodamnia cinerea and uses thereof
US8569282B2 (en) 2007-12-11 2013-10-29 Cytopathfinder, Inc. Carboxamide compounds and their use
WO2014170786A1 (en) 2013-04-17 2014-10-23 Pfizer Inc. N-piperidin-3-ylbenzamide derivatives for treating cardiovascular diseases
US8877267B2 (en) 2004-05-10 2014-11-04 University Of Copenhagen Flaxseeds for body weight management
WO2016055901A1 (en) 2014-10-08 2016-04-14 Pfizer Inc. Substituted amide compounds
WO2013167995A3 (en) * 2012-05-08 2016-09-01 Cellixbio Private Limited Compositions and methods for the treatment of hyperglycemia
US10500245B2 (en) 2014-02-18 2019-12-10 Universite De La Rochelle Compositions for preventing and/or treating pathological conditions associated with alpha-glucosidase
WO2020150473A2 (en) 2019-01-18 2020-07-23 Dogma Therapeutics, Inc. Pcsk9 inhibitors and methods of use thereof

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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DE19802700A1 (en) * 1998-01-24 1999-07-29 Bayer Ag Preparation of fast-dissolving tablets for controlling blood sugar levels
EP1470116A4 (en) 2001-12-04 2005-04-06 Biogal Gyogyszergyar Preparation of orlistat and orlistat crystalline forms
FI20045076A7 (en) * 2004-03-15 2005-09-16 Bioferme Oy Functional food
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EP2002825B1 (en) * 2007-06-14 2013-05-22 Krka Pharmaceutical compositions comprising orlistat
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RU2441654C2 (en) * 2010-02-17 2012-02-10 Лабораториос Баго С.А. Pharmaceutical composition having anti-obesity activity containing the premix of pure orlistat and the way of its manufacturing
TR201100148A2 (en) * 2011-01-06 2012-07-23 Bi̇lgi̇ç Mahmut Stable acarbose formulations.
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Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4189438A (en) * 1977-02-08 1980-02-19 Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai Physiologically active substance esterastin
US4254256A (en) * 1977-12-28 1981-03-03 Toyo Jozo Company, Ltd. Amino sugar compound
US4273765A (en) * 1978-02-14 1981-06-16 Hoffmann-La Roche Inc. Amino sugar derivatives containing trehalose
US4358602A (en) * 1980-03-14 1982-11-09 Zaidan Hojin Biseibutsu Kagaku Kenkyu Kao Ebelactones and production thereof
EP0129748A1 (en) * 1983-06-22 1985-01-02 F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft Hexadecanoic acid and hexadecadienoic-acid derivatives
US4623714A (en) * 1984-01-21 1986-11-18 Hoechst Aktiengesellschaft Novel polypeptides with an α-amylase-inhibiting action, a process for their preparation, their use and pharmaceutical products
WO1989011295A1 (en) * 1988-05-09 1989-11-30 Pierre Demeyts Inhibition of lipogenesis
EP0364696A2 (en) * 1988-08-22 1990-04-25 Takeda Chemical Industries, Ltd. Alpha-glucosidase inhibitor as a calcium absorption promotor
WO1992005788A1 (en) * 1990-10-09 1992-04-16 Novo Nordisk A/S New phosphonate derivatives as lipase agents inhibiting
WO1993007872A1 (en) * 1991-10-17 1993-04-29 The University Of Nottingham Lysosomal enzyme inhibitors for the treatment of neurodegenerative diseases
US5240962A (en) * 1991-04-15 1993-08-31 Takasago Institute For Interdisciplinary Science, Inc. Antiobesity and fat-reducing agents

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA824382B (en) * 1981-07-07 1984-02-29 Wyeth John & Brother Ltd Anti-obesity agents
US4632925A (en) * 1985-10-07 1986-12-30 Hoffmann-La Roche Inc. N-substituted diphenylpiperidines and antiobesity use thereof
SU1697823A1 (en) * 1988-08-01 1991-12-15 Киевский государственный институт усовершенствования врачей Method for alimentary-constitutional obesity treatment

Patent Citations (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4189438A (en) * 1977-02-08 1980-02-19 Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai Physiologically active substance esterastin
US4254256A (en) * 1977-12-28 1981-03-03 Toyo Jozo Company, Ltd. Amino sugar compound
US4273765A (en) * 1978-02-14 1981-06-16 Hoffmann-La Roche Inc. Amino sugar derivatives containing trehalose
US4358602A (en) * 1980-03-14 1982-11-09 Zaidan Hojin Biseibutsu Kagaku Kenkyu Kao Ebelactones and production thereof
EP0129748A1 (en) * 1983-06-22 1985-01-02 F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft Hexadecanoic acid and hexadecadienoic-acid derivatives
US4598089A (en) * 1983-06-22 1986-07-01 Hoffmann-La Roche Inc. Leucine derivatives
US4623714A (en) * 1984-01-21 1986-11-18 Hoechst Aktiengesellschaft Novel polypeptides with an α-amylase-inhibiting action, a process for their preparation, their use and pharmaceutical products
WO1989011295A1 (en) * 1988-05-09 1989-11-30 Pierre Demeyts Inhibition of lipogenesis
US4952567A (en) * 1988-05-09 1990-08-28 City Of Hope Inhibition of lipogenesis
EP0364696A2 (en) * 1988-08-22 1990-04-25 Takeda Chemical Industries, Ltd. Alpha-glucosidase inhibitor as a calcium absorption promotor
US5036081A (en) * 1988-08-22 1991-07-30 Takeda Chemical Industries, Ltd. Calcium absorption promoter
WO1992005788A1 (en) * 1990-10-09 1992-04-16 Novo Nordisk A/S New phosphonate derivatives as lipase agents inhibiting
US5240962A (en) * 1991-04-15 1993-08-31 Takasago Institute For Interdisciplinary Science, Inc. Antiobesity and fat-reducing agents
WO1993007872A1 (en) * 1991-10-17 1993-04-29 The University Of Nottingham Lysosomal enzyme inhibitors for the treatment of neurodegenerative diseases

Non-Patent Citations (29)

* Cited by examiner, † Cited by third party
Title
Annual Drug Data Report (Published by Prous, Barcelona, Spain) (1986) 8( ), 558. *
Annual Drug Data Report (Published by Prous, Barcelona, Spain) (1986) 8(?), 558.
Annual Drug Data Report (Published by Prous, Barcelona, Spain) (1986) 8(3), 276. *
Annual Drug Data Report (Published by Prous, Barcelona, Spain) (1987) 9(7), 603. *
Annual Drug Data Report (Published by Prous, Barcelona, Spain) (1990) 12(8), 636. *
Annual Drug Data Report (Published by Prous, Barcelona, Spain) (1992) 14(1), 46. *
Annual Drug Data Report (Published by Prous, Barcelona, Spain) (1992) 14(7) 610. *
Annual Drug Data Report (Published by Prous, Barcelona, Spain) (1992) 14(7), 606. *
Annual Drug Data Report Dept. 1991, pp. 590 591. *
Annual Drug Data Report Dept. 1991, pp. 590-591.
Annual Drug Data Report p. 167 (1985). *
Annual Drug Data Report p. 723 (1992). *
Annual Drug Report p. 343 (1987). *
Antidiabetic Agents, 30th Edition, Martindale Extra Pharmacopoeia, 276, no date available. *
B.W. Bycroft, Dictionary of Antibiotics and Related Substances, 1988, Champman and Hall, London, New York, pp. 15; 298; 315; 445; 698. *
Federation Proceedings (1982) 41(3), 698. *
Hauptman et al., Initial Studies in Humans with the Novel Gastrointestinal Lipase Inhibitor Ro 18 0646 (tetrahydro lipstatin) 1,2 , Am. J. Nutr. 1992:55:309S 313S. *
Hauptman et al., Initial Studies in Humans with the Novel Gastrointestinal Lipase Inhibitor Ro 18-0646 (tetrahydro-lipstatin)1,2, Am. J. Nutr. 1992:55:309S-313S.
Int. J. Obesity, 1992; 16 (Suppl. 1):16, Abstr. 063. *
J. Antibiot. XL (1987) pp. 1647 1650. *
J. Antibiot. XL (1987) pp. 1647-1650.
J. Antibiotics XXXI No. 8, Kondo, et al., 1978. *
J. of Antibiotics vol. 35, No. 9 (1982) pp. 1160 1166. *
J. of Antibiotics vol. 35, No. 9 (1982) pp. 1160-1166.
Lehninger, Biochemistry, Second Edition, Worth Publishers, Inc., New York: 1975, p. 265. *
M. Negwer, Organic Chemical Drugs and Their Synonyms, 6. Auflage, vol. II 1987, pp. 1310; 1311; 1547; 1652. *
M. Negwer, Organic-Chemical Drugs and Their Synonyms, 6. Auflage, vol. II 1987, pp. 1310; 1311; 1547; 1652.
Merck Index, 11th Ed. 1989 p. 4. *
WHO Chronicle (1980) 34 (Suppl.). *

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6147108A (en) * 1997-02-05 2000-11-14 Hoffman-La Roche Inc. Method for treating type II diabetes mellitus
US6004996A (en) * 1997-02-05 1999-12-21 Hoffman-La Roche Inc. Tetrahydrolipstatin containing compositions
US6403641B2 (en) 1997-12-24 2002-06-11 Abbott Labortories Therapeutic agents
US6358522B1 (en) * 1998-08-14 2002-03-19 Hoffmann-La Roche Inc. Pharmaceutical compositions containing lipase inhibitor
WO2000013667A1 (en) * 1998-09-08 2000-03-16 Smithkline Beecham Corporation Lipstatin derivative-soluble fiber tablets
US7393545B2 (en) 1998-09-08 2008-07-01 Smithkline Beecham Corporation Lipstatin derivative—soluble fiber tablets
US6607749B1 (en) 1998-09-08 2003-08-19 Smithkline Beecham Corporation Lipstatin derivative-soluble fiber tablets
WO2000043036A3 (en) * 1999-01-22 2001-11-01 Hunza Di Maria Carmela Marazzi Lipoprotein complexes and compositions containing them
US6340669B1 (en) 1999-01-22 2002-01-22 Hunza Di Maria Carmela Marazzita S.A.S. Lipoprotein complexes and compositions containing them
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US20040175420A1 (en) * 1999-09-13 2004-09-09 De Smidt Passchier Christiaan Pharmaceutical compositions containing lipase inhibitors
US8012494B2 (en) 1999-09-13 2011-09-06 Hoffmann-La Roche Inc. Pharmaceutical compositions containing lipase inhibitors
US6342519B2 (en) * 1999-10-29 2002-01-29 2 Pro Chemical Oxetanone derivatives
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US6756364B2 (en) 2000-07-28 2004-06-29 Hoffmann-La Roche Inc. Method of reducing gastrointestinal side effects associated with orlistat treatment
US20050136030A1 (en) * 2000-07-28 2005-06-23 Pierre Barbier Orlistat compositions
US20040105838A1 (en) * 2000-07-28 2004-06-03 Pierre Barbier Orlistat compositions
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US20030138396A1 (en) * 2000-07-28 2003-07-24 Paul Hadvary Method of treating high plasma cholesterol levels
US8071571B2 (en) 2000-07-28 2011-12-06 Hoffman-La Roche Inc. Orlistat compositions
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US6562329B2 (en) 2000-07-28 2003-05-13 Hoffmann-La Roche Inc. Method of treating high plasma cholesterol levels
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US7713546B1 (en) 2001-04-03 2010-05-11 Soft Gel Technologies, Inc. Corosolic acid formulation and its application for weight-loss management and blood sugar balance
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WO2002083153A1 (en) * 2001-04-10 2002-10-24 Morrison James U Method and composition for controlled release acarbose formulations
US7108869B2 (en) 2002-11-07 2006-09-19 Access Business Group International Llc Nutritional supplement containing alpha-glucosidase and alpha-amylase inhibitors
US20040091554A1 (en) * 2002-11-07 2004-05-13 Murray Mary A. Nutritional supplement containing alpha-glucosidase and alpha-amylase inhibitors
US20050208161A1 (en) * 2002-11-07 2005-09-22 Access Business Group International Llc Nutritional supplement containing alpha-glucosidase and alpha-amylase inhibitors
US7354606B2 (en) 2002-11-07 2008-04-08 Access Business Group International Llc Nutritional supplement containing alpha-glucosidase and alpha-amylase inhibitors
US7649002B2 (en) 2004-02-04 2010-01-19 Pfizer Inc (3,5-dimethylpiperidin-1yl)(4-phenylpyrrolidin-3-yl)methanone derivatives as MCR4 agonists
US20060202077A1 (en) * 2004-05-07 2006-09-14 Enventys, Llc Independently drawing and tensioning lines with bi-directional rotary device having two spools
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US20060111422A1 (en) * 2004-11-23 2006-05-25 Warner-Lambert Company Llc Novel pyrazole-based HMG CoA reductase inhibitors
US7446121B2 (en) 2004-11-23 2008-11-04 Pfizer Inc. Pyrazole-based HMG CoA reductase inhibitors
US8283312B2 (en) 2005-02-04 2012-10-09 The Research Foundation Of State University Of New York Compositions and methods for modulating body weight and treating obesity-related disorders
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